| Abstract
| - This paper reports the study of some 2-arylpyrazolo[3,4-c]quinolin-4-ones, 4-amines, and 4-amino-substitutedderivatives designed as human A3 adenosine receptor (AR) antagonists. Most of the herein reported compoundsshowed a nanomolar affinity toward the hA3 receptor subtype and different degrees of selectivity that resultedto be strictly dependent on the presence and nature of the substituent on the 4-amino group. Bulky andlipophilic acyl groups, as well as the benzylcarbamoyl residue, afforded highly potent and selective hA3receptor antagonists. The selected 4-diphenylacetylamino-2-phenylpyrazoloquinoline (25) and 4-dibenzoylamino-2-(4-methoxyphenyl)pyrazoloquinoline (36), tested in an in vitro rat model of cerebral ischemia,prevented the irreversible failure of synaptic activity induced by oxygen and glucose deprivation in thehippocampus. The observed structure−affinity relationships of this class of antagonists were also exhaustivelyrationalized using the recently published ligand-based homology modeling (LBHM) approach.
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